Acetaminophen + chronic/acute alcohol mechanism of liver damage

[Leonidis I]

Ok so I get that chronic alcoholism = P450 inducer = acetaminophen rapidly metabolized to free radical, uses up all the glutathione, causes damage, etc. etc.

but what is the mechanism of damage to the liver with acute alcohol (which is a P450 inhibitor) + acetaminophen. The acute alcohol isn't inducing the P450 like chronic alcohol so it can't be the same mechansism.

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[Oblique]

Ok so I get that chronic alcoholism = P450 inducer = acetaminophen rapidly metabolized to free radical, uses up all the glutathione, causes damage, etc. etc.

but what is the mechanism of damage to the liver with acute alcohol (which is a P450 inhibitor) + acetaminophen. The acute alcohol isn't inducing the P450 like chronic alcohol so it can't be the same mechansism.

I think acute ETOH ingestion may be protective of acetaminophen overdose, because it decreases acetaminophen metabolism to NAPQI.

 

[CherryRedDracul]

As far as I know, theoretically, chronic alcohol usage predisposes you to acetaminophen toxicity and acute alcohol ingestion may have a protective effect by inhibited CYP2E1. To be honest, I don't know much about it beyond that.

 

[HatWobble]

I think acute ETOH ingestion may be protective of acetaminophen overdose, because it decreases acetaminophen metabolism to NAPQI.

As far as I know, theoretically, chronic alcohol usage predisposes you to acetaminophen toxicity and acute alcohol ingestion may have a protective effect by inhibited CYP2E1. To be honest, I don't know much about it beyond that.

Yep. ETOH consumption induces expression of CYP2E1. Drinking followed by acetaminophen several hours later (i.e. what most of us do) leads to faster metabolism of acetaminophen into NAPQI, leading to increased toxicity. Taking alcohol after acetaminophen actually reduces toxicity because it occupies CYP2E1 and inhibits NAPQI production.